title: Elevated antisaccade error rate as an intermediate phenotype for psychosis across diagnostic categories.
abstract: BACKGROUND
  Elevated antisaccade error rate, reflecting problems with inhibitory behavioral control, is a promising intermediate phenotype for schizophrenia. Here, we consider whether it marks liability across psychotic disorders via common or different neurophysiological mechanisms and whether it represents a neurocognitive risk indicator apart from the generalized cognitive deficit.
  
  
  METHODS
  Schizophrenia (n = 267), schizoaffective (n = 150), and psychotic bipolar (n = 202) probands, their first-degree relatives (ns = 304, 193, 242, respectively), and healthy controls (n = 244), participating in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium, performed antisaccade and prosaccade tasks and completed a neuropsychological battery.
  
  
  RESULTS
  Antisaccade error rate was elevated in proband groups with greatest deficit observed in schizophrenia and was unrelated to symptoms and antipsychotic treatment. Increased error rate was also observed among relatives, even those without history of psychosis or psychosis spectrum personality traits. Relatives' deficits were similar across proband diagnoses. Error rate was familial and remained elevated in proband and relative groups after accounting for generalized cognitive impairment. Speed of attentional shifting, indexed by prosaccade latency, was similarly influenced in all groups by manipulations that freed vs increasingly engaged attention systems and was inversely associated with antisaccade error rate in all but schizophrenia probands.
  
  
  CONCLUSIONS
  These findings indicate that elevated antisaccade error rate represents an intermediate phenotype for psychosis across diagnostic categories, and that it tracks risk beyond that attributable to the generalized cognitive deficit. The greater severity of antisaccade impairment in schizophrenia and its independence from attention shifting processes suggest more severe and specific prefrontal inhibitory control deficits in this disorder.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL; james.reilly@northwestern.edu.
authors.forename: James L
authors.initials: JL
authors.lastname: Reilly
authors.affiliation: Center for Mind and Brain and Department of Psychology, University of California at Davis, Davis, CA;
authors.forename: Kyle
authors.initials: K
authors.lastname: Frankovich
authors.affiliation: Department of Psychology, Rosalind Franklin University of Medicine and Science, Chicago, IL;
authors.forename: Scot
authors.initials: S
authors.lastname: Hill
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL;
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Gershon
authors.affiliation: Department of Psychiatry, Duke University, Durham, NC;
authors.forename: Richard S E
authors.initials: RS
authors.lastname: Keefe
authors.affiliation: Beth Israel Deaconess Hospital and Massachusetts Mental Health Center, Harvard Medical School, Boston, MA;
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.affiliation: Olin Neuropsychiatry Research Center, Yale School of Medicine, New Haven, CT; Department of Psychiatry, Institute of Living/Hartford Hospital, Hartford, CT;
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.affiliation: Department of Psychiatry, UT Southwestern Medical School, Dallas, TX.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
authors.affiliation: Department of Psychiatry, UT Southwestern Medical School, Dallas, TX.
authors.forename: John A
authors.initials: JA
authors.lastname: Sweeney
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000503:physiopathology*; D058068:Endophenotypes; D056344:Executive Function / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D011597:Psychomotor Performance / Q000502:physiology*; D011618:Psychotic Disorders / Q000235:genetics / Q000503:physiopathology*; D012438:Saccades / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology*
keywords: bipolar disorder; endophenotype; family study; schizoaffective disorder; schizophrenia